The 90 kDa heat shock protein (hsp90) is a highly abundant, highly conserved protein in both prokaryotes and eukaryotes. Like several other heat shock proteins, hsp90 has been shown to chaperone protein folding in vitro. In addition, hsp90 modulates the activities of a variety of signal transduction molecules including steroid hormone receptors as well as nonreceptor tyrosine kinases (such as v-src). Overall, the studies of the interactions between hsp90 and these signal transduction molecules hint that the mechanism through which hsp90 modulates the functions of these molecules and its role as a chaperone may overlap; these signaling molecules may have co-opted the ability of hsp90 to stabilize folding intermediates into regulating conformational changes necessary for signaling. Therefore, we have initiated a structural study of htpG, the E. coli member of the hsp90 family.